1. Field of the Invention
This invention relates to a process of chromatographic separation and, more particularly, to a process for chromatographically separating a fluid mixture comprising two or more components into two or more fractions enriched in the respective components.
2. Description of the Related Art
Chromatographic separation techniques using solid adsorbents are extensively conducted in industries. Various techniques of chromatographic separation have been proposed for separating a mixture of two or more components into fractions enriched in each component.
Among chromatographic separation systems is a simulated moving-bed system, which is widely used in industries for its excellent separation performance and high productivity. In this system a feedstock fluid or a desorbent is supplied to a packed bed at a constant flow rate, and the fluid flows through the packed bed also at a constant flow rate. The simulated moving-bed system, however, requires complicated apparatus and high skill of control on the supply of a feedstock fluid or a desorbent to the packed bed and on the movement of the fluid circulating through the packed bed. While the simulated moving-bed system shows excellent performance in separating a mixture into two fractions, great difficulty has been encountered with this system in achieving separation into three or more fractions.
Chromatographic separation processes, which can achieve satisfactory separation results with simpler apparatus, have been proposed as disclosed in JP-A-63-158105 (corresponding to U.S. Pat. No. 4,970,002 and Canadian Patent No. 1305434) and JP-A-2-49159. The process disclosed in JP-A-63-158105, for example, comprises repetition of cycles each including at least three steps; a step of supplying a feedstock fluid, a step of supplying a desorbent fluid, and a step of circulating the fluid in the packed bed.
In the simulated moving-bed system, the concentration distribution curves made in the packed bed macroscopically have almost the same form and circulatively move through the packed bed with time while keeping the form. Accordingly, the pressure required for moving the fluid through the packed bed, namely, the pressure drop (pressure loss) produced while the liquid moves from the upstream end to the downstream end of the packed bed may be seen substantially equal in any time zone. In this situation, the above-described process control relying on a constant flow rate is an effective system for controlling the apparatus with good reproducibility to obtain desired separation performance.
According to the method of JP-A-63-158105, the flow rate of the feedstock liquid and the desorbent fluid while being supplied and the flow rate of the liquid moving through the packed bed are controlled at a prescribed rate, and switches among the steps are made for a certain amount of the liquid or for a certain lapse of time. In this case, however, the concentrations of the individual components in the packed bed and the concentration distributions formed in the bed gradually vary with time in every step. More specifically, in the step wherein the feed stock fluid is supplied while a fraction enriched in a certain component is withdrawn, the concentration of the components present in the packed bed gradually increases from start to stop of the supply, and the feedstock is distributed in its maximum concentration in the packed bed to which it is supplied. In the step where the desorbent is supplied while a fraction enriched in another certain component is withdrawn, the concentration of the components present in the packed bed gradually decreases from start to stop of the supply. In other words, the feedstock supplied to the packed bed gradually decreases its concentration as it flows downstream. Even in the step where the fluid is moved circulatively with no liquid supplied nor withdrawn thereby to allow a zone in which a plurality of components are present in admixture to move to the upstream end of the packed bed, the concentration distribution in the packed bed gradually changes from start to stop of the step.
A mixture of saccharides (i.e., a carbohydrate solution including various kinds of sugars and/or sugar alcohols) is one of the most common feedstock fluid to be treated by chromatographic separation. In the present invention, the mixture of saccharides means a mixture solution of at least two selected from the group consisting of sugars and sugar alcohols. A mixture of saccharides greatly varies its viscosity depending on the concentration, and a higher concentration mixture has a higher viscosity. In treating such a fluid like a saccharides mixture as would greatly vary its viscosity according to the concentration, variations in concentrations of, or concentration distributions of, the components present in the packed bed necessitate variations of the pressure for moving the fluid through the bed at a constant rate. In other words, the pressure drop generated in moving the fluid in an upstream packed bed to which the feedstock fluid is supplied, being expressed in terms of pressure drop per unit height of the packed bed (hereinafter xe2x80x9cunit pressure dropxe2x80x9d), is different from that in a packed bed positioned downstream. That is, the packed bed to which the feedstock fluid is supplied shows a greater unit pressure drop than any other packed bed.
The changes in pressure drop are analyzed as follows. In the supply step in which a feedstock fluid containing a plurality of components is fed, a fluid having a lower concentration than the feedstock fluid and enriched in a certain component is withdrawn. Accordingly, the average concentration of the components in the bed gradually increases during this step. In the step of supplying the desorbent and withdrawing another fraction enriched in another certain component, the fluid withdrawn is obviously higher in concentration than the desorbent. This means that the average concentration of the components present in the packed bed is gradually decreasing in this desorption step. The feedstock fluid supplied moves through the packed bed with a descending unit pressure drop. In general, a maximum unit pressure drop is reached in the packed bed where the feedstock is supplied at about the end of the step of feeding the feedstock fluid.
Apparatus used in the above-described chromatographic separation processes including the simulated moving-bed system comprise a plurality of unit beds packed with an adsorbent selected according to the components to be separated. Cation-exchange resins have been in frequent use as an adsorbent. Because the purity or recovery of a component separated or recovered is greatly influenced by the properties of a chosen cation-exchange resin, various attempts have been made in making a choice of an adsorbent. For example, it has been proposed to use ion-exchangers having different ionic forms fit for the individual components or to use a combination of two or more kinds of adsorbents in separating a feedstock comprising three or more components into the individual fractions (see JP-A-11-183459 and JP-A-11-267404).
In order to improve separation efficiency of a chromatographic separation apparatus having a plurality of unit packed beds, it is generally preferred that every bed is packed with an ion-exchange resin having a small average particle size and/or a low degree of crosslinking. However, an adsorbent having a smaller particle size makes the unit pressure drop greater, and a resin having a lower degree of crosslinking has lower strength.
The method of JP-A-63-158105 supra employs an apparatus comprising a packed bed to which a feedstock fluid is supplied and other packed bed(s). As previously noted, where a feedstock fluid largely varies its viscosity with concentration as with the case of a saccharides mixture, the unit pressure drop reaches the maximum in the packed bed to which the feedstock fluid is supplied. The pressure applied to the fluid imposes a mechanical force on the adsorbent, i.e., an ion-exchange resin, as a friction pressure to substantively influence shape retention of the ion-exchange resin. In a worst case, the resin is ruptured by the force.
Where the ion-exchange resin of a packed bed to which a feedstock fluid is supplied has a small average particle size, the packed bed exhibits a large pressure drop factor (friction factor) to cause a high unit pressure drop. Further, an ion-exchange resin having a low degree of crosslinking has relatively low mechanical strength so that a pressure above a certain level tends to cause compaction. As a result, the pressure drop increases at an increasing rate, and rupture of the resin particles can result.
There is a trend to use ion-exchange resins of small particle size and low degree of crosslinking for obtaining desired separation performance. However, to use such ion-exchange resins, while making no particular problem in small-scale apparatus, will cause a great hindrance in securing desired separation performance with large apparatus of industrial scale for an extended period of time and is also economically problematic because of large energy required to move liquid (i.e., the high running cost).
The present inventors have confirmed that using an ion-exchange resin having an increased average particle size or an increased degree of crosslinking as an adsorbent to be packed into a separation column to which a feedstock fluid is supplied does not impair the separation performance of the whole separation system because the degree of separation in this packed bed is low.
An object of the present invention is to provide an improvement comprising using an adsorbent (especially an ion-exchange resin) having specific physical properties in a chromatographic separation process for separating a feedstock fluid comprising a plurality of components into fractions enriched in the individual components, the process involving variations in concentration and concentration distribution of the components of the feedstock fluid in the unit packed beds.
The concept of the present invention resides in controlling the relationship in physical properties between the adsorbent, e.g., an ion-exchange resin, which is used in a unit packed bed to which the feedstock fluid is supplied and the adsorbent which is used in the other unit packed bed(s).
The present invention provides a chromatographic separation process of a type wherein a feedstock fluid containing a plurality of components having different degrees of affinity for an adsorbent and a desorbent are alternately supplied into a chromatographic separation system in which the downstream end of a bed packed with the adsorbent is connected to its upstream end by a piping to enable the fluid to flow circulatively from the upstream end of the packed bed to its downstream end to form adsorption zones having the concentration distribution of the respective components and to withdraw therefrom a plurality of fractions different in components fromthe feedstock fluid, the process including the steps of:
(i) supplying the feedstock fluid into the packed bed at its upstream end while withdrawing a fraction enriched in a first component from the downstream end of the bed,
(ii) supplying the desorbent fluid into the packed bed at its upstream end while withdrawing a fraction enriched in a second component from the downstream end of the bed, and
(iii) circulating the fluid in the bed from the downstream end of the packed bed through the piping to its upstream end without supplying or withdrawing any fluid into or from the packed bed, thereby making a mixed zone where the first component withdrawn in step (i) and the second component are present in admixture move to the upstream end of the packed bed, the steps (i) to (iii) being performed cyclically and repeatedly, wherein;
the packed bed comprises a plurality of unit beds packed with an adsorbent, e.g., an ion-exchange resin, and the adsorbent packed into the unit bed to which the feedstock fluid is supplied has a greater average particle size than that packed in any other unit packed bed and/or has a higher degree of crosslinking than that packed in any other unit packed bed.
In a preferred embodiment of the invention, i) the adsorbent packed into the unit bed to which the feedstock fluid is supplied has a greater average particle size than that packed in any other unit packed bed, when the adsorbent packed into the unit bed to which the feedstock fluid is supplied has the same degree of crosslinking as that packed in any other unit packed bed, ii) the adsorbent packed into the unit bed to which the feedstock fluid is supplied has a higher degree of crosslinking than that packed in any other unit packed bed, when the adsorbent packed into the unit bed to which the feedstock fluid is supplied has the same average particle size as that packed in any other unit packed bed, or iii) the adsorbent packed into the unit bed to which the feedstock fluid is supplied has a greater average particle size than that packed in any other unit packed bed and has a higher degree of crosslinking than that packed in any other unit packed bed.
In a preferred embodiment of the invention, the adsorbent, e.g., an ion-exchanged resin, in the unit packed bed to which the feedstock fluid is supplied is 1.2 to 2.0 times as large as the adsorbent(s) in the other unit packed beds in average particle size. In another preferred embodiment of the invention, the volume of the adsorbent, e.g., an ion-exchange resin, in the unit packed bed to which the feedstock fluid is supplied is xe2x85x9 to xc2xd of the total volume of the adsorbents of all the unit packed beds, and the adsorbent packed into the unit bed to which the feedstock fluid is supplied has a greater average particle size than that packed in any other unit packed bed and/or has a higher degree of crosslinking than that packed in any other unit packed bed. The chromatographic separation process of the invention is particularly fit for separating a mixture of saccharides (a carbohydrate solution).